tbuckley/cabot-search huggingface dataset:
Taxanes plus cetuximab with or without platinum chemotherapy after progression on immune checkpoint inhibitors in patients with squamous cell carcinoma of the head and neck.
Authors: Khalil Saleh, Marie Vinches, Inga Safta, Emeline Guiard, Gregoire Marret, Roman Vion, Joel Guigay, François-Régis Ferrand, Florian Clatot, Christophe Le Tourneau, Audrey Rambeau, Esma Saada-Bouzid, Amaury Daste, Caroline Even
Journal: Journal of Clinical Oncology (2022)

6036 Background: Salvage chemotherapy after progression on immune checkpoint inhibitors (ICIs) was associated with an objective response rate (ORR) of 30% in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). We aimed to investigate the efficacy of taxanes + cetuximab (TC) +/- platinum chemotherapy in pts with R/M SCCHN who failed ICIs in palliative setting. Methods: A retrospective study was conducted at 7 French university hospitals. Eligibility criteria were pts treated with ICI for R/M SCCHN, who progressed after treatment with ICI and received TC +/- platinum salvage chemotherapy between August 2017 and December 2021. Clinical and radiological data and outcome were collected from review of medical records. Results: Ninety-nine pts met eligibility criteria: 63 pts received TC and 36 pts received triplet regimen (TR). The median age was 61 years (range 24-78) and 79% of pts were male. Forty-two pts (42%) had platinum-refractory disease (PRD) after multimodal treatment, 13 pts received prior taxanes and 24 pts received prior cetuximab. The median PS at salvage chemotherapy was 1 (range 0-3). ICIs were given as first-line treatment in 70% of pts including those with PRD. The ORR of the entire cohort was 62% (61/99) including 5 complete responses (CR) and the disease control rate was 79% (78/99). The median progression-free survival of the entire cohort was 4.4 months and the median overall survival (OS) was 7.5 months. The 5 pts who had CR as best response are still in remission after a median follow-up of 24 months (range 8-58). The ORR of TC subgroup was 57% (36/63) and the ORR of TR subgroup was 69% (25/36). Furthermore, the ORR in the PRD subgroup of pts was 54% (39/72), and the ORR in the subgroup of pts who were not chemo naïve was 54% (39/72). The ORR in pts who previously received cetuximab was 50% (12/24) vs 75% (49/75) in those who did not. The ORR in pts who previsouly received taxanes was 38% (5/13) vs 65% in those who did not. Finally, the ORR in PRD pts and treated with TR was 50% (7/14) and the ORR in pts who previously received platinum-based treatment or PRD and treated with TR was 55% (11/20). Conclusions: TC +/- platinum chemotherapy was highly effective in pts R/M SCCHN who progressed on ICIs with an ORR of 62% and DCR of 79%. Further investigations are warranted.
Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study.
Authors: Shanu Modi, William Jacot, Toshinari Yamashita, Joohyuk Sohn, Maria Vidal, Eriko Tokunaga, Junji Tsurutani, Naoto T. Ueno, Yee Soo Chae, Keun Seok Lee, Naoki Niikura, Yeon Hee Park, Xiaojia Wang, Binghe Xu, Dhiraj Gambhire, Lotus Yung, Gerold Meinhardt, Yibin Wang, Nadia Harbeck, David A. Cameron
Journal: Journal of Clinical Oncology (2022)

LBA3 Background: About 55% of mBC typically categorized as HER2 negative, express low levels of HER2 (IHC 1+ or IHC 2+/ISH− by ASCO/CAP 2018 guidelines) with poor outcomes in later lines (Tarantino 2020). T-DXd has shown promising efficacy in HER2-low mBC in a phase 1 study (NCT02564900; Modi 2020). This is the primary report from DESTINY-Breast04 (NCT03734029), the first randomized, multicenter, open-label, phase 3 study comparing efficacy and safety of T-DXd vs TPC in pts with HER2-low mBC treated with 1-2 prior lines of chemotherapy in the metastatic setting. Methods: 557 pts with centrally confirmed HER2-low mBC were randomly assigned 2:1 to T-DXd 5.4 mg/kg or TPC (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel). The primary endpoint was progression-free survival (PFS) determined by blinded independent central review (BICR) in pts with hormone receptor–positive (HR+) mBC. Key secondary endpoints (hierarchically tested after the primary endpoint) include PFS by BICR in the full analysis set (FAS; HR+/−) and overall survival (OS) in pts with HR+ mBC and in FAS. Other endpoints were objective response rate, duration of response, safety, and an exploratory analysis of pts with HR− mBC. Results: As of Jan 11, 2022, 373 and 184 pts (88.7% and 88.6% HR+ mBC) were assigned to T-DXd and TPC, respectively. Median follow-up was 18.4 months (mo; 95% CI, 17.9-19.1). Median treatment duration was 8.2 mo (range, 0.2-33.3) with T-DXd and 3.5 mo (range, 0.3-17.6) with TPC. Efficacy results are in the Table. 52.6% of pts with T-DXd vs. 67.4% of pts with TPC had grade (G) ≥ 3 treatment-emergent adverse events (TEAEs). With T-DXd, 45 pts (12.1%; 10.0% G1/2, 1.3% G3/4, 0.8% G5) had independently adjudicated drug-related interstitial lung disease [ILD]/pneumonitis vs. 1 pt (0.6% G1) with TPC. Conclusions: DESTINY-Breast04 is the first phase 3 trial of a HER2-directed therapy in pts with HER2-low mBC to show a statistically significant and clinically meaningful benefit in PFS and OS compared to standard-of-care treatment, regardless of HR status, with a generally manageable safety profile. Funding: Daiichi Sankyo, Inc., and AstraZeneca. Clinical trial information: NCT03734029. [Table: see text]
Impact of ischaemic aetiology on the efficacy of intravenous ferric carboxymaltose in patients with iron deficiency and acute heart failure: insights from the AFFIRM‐AHF trial
Authors: Marco Metra, Ewa A. Jankowska, Matteo Pagnesi, Stefan D. Anker, Javed Butler, Fabio Dorigotti, Vincent Fabien, Gerasimos Filippatos, Bridget‐Anne Kirwan, Iain C. Macdougall, Giuseppe Rosano, Frank Ruschitzka, Daniela Tomasoni, Peter van der Meer, Piotr Ponikowski
Journal: European Journal of Heart Failure (2022)

Aims In AFFIRM‐AHF, intravenous ferric carboxymaltose (FCM) reduced heart failure (HF) hospitalisations and improved quality of life versus placebo in iron‐deficient patients stabilised after an acute HF episode. This analysis explored the effects of FCM versus placebo in patients with ischaemic and non‐ischaemic HF aetiology. Methods and results We included 1082 patients from AFFIRM‐AHF: 590 with ischaemic HF (defined as investigator‐reported ischaemic HF aetiology and/or prior acute myocardial infarction and/or prior coronary revascularisation) and 492 with non‐ischaemic HF. The prevalences of male sex, comorbidities, and history of HF were higher in the ischaemic versus non‐ischaemic HF subgroup. Annualised event rates for the primary composite outcome of total HF hospitalisations and cardiovascular death with FCM versus placebo were 65.3 versus 100.6 per 100 patient‐years in the ischaemic HF subgroup (rate ratio [RR] 0.65, 95% confidence interval [CI] 0.47–0.89, p = 0.007) and 58.3 versus 52.5 in the non‐ischaemic HF subgroup (RR 1.11, 95% CI 0.75–1.66, p = 0.60) ( p interaction = 0.039). An interaction between HF aetiology and treatment effect was also observed for the secondary outcome of total HF hospitalisations ( p interaction = 0.038). A nominal increase in quality of life, assessed using the 12‐item Kansas City Cardiomyopathy Questionnaire, was observed with FCM versus placebo, within each subgroup. Conclusions Heart failure hospitalisations and cardiovascular deaths occurred at a higher rate in patients with ishaemic versus those with non‐ischaemic HF and were reduced by FCM versus placebo only in ischaemic patients. Further studies are needed to assess the role of aetiology in FCM efficacy.
Cutaneous manifestations of SARS-CoV-2 infection during the Delta and Omicron waves in 348 691 UK users of the UK ZOE COVID Study app
Authors: Alessia Visconti, Benjamin Murray, Niccolò Rossi, Jonathan Wolf, Sebastien Ourselin, Tim D. Spector, Esther E. Freeman, Veronique Bataille, Mario Falchi
Journal: British Journal of Dermatology (2022)

Symptoms of SARS-CoV-2 infection have differed during the different waves of the pandemic but little is known about how cutaneous manifestations have changed.To investigate the diagnostic value, frequency and duration of cutaneous manifestations of SARS-CoV-2 infection and to explore their variations between the Delta and Omicron waves of the pandemic.In this retrospective study, we used self-reported data from 348 691 UK users of the ZOE COVID Study app, matched 1 : 1 for age, sex, vaccination status and self-reported eczema diagnosis between the Delta and Omicron waves, to assess the diagnostic value, frequency and duration of five cutaneous manifestations of SARS-CoV-2 infection (acral, burning, erythematopapular and urticarial rash, and unusual hair loss), and how these changed between waves. We also investigated whether vaccination had any effect on symptom frequency.We show a significant association between any cutaneous manifestations and a positive SARS-CoV-2 test result, with a diagnostic value higher in the Delta compared with the Omicron wave (odds ratio 2·29, 95% confidence interval 2·22-2·36, P < 0·001; and odds ratio 1·29, 95% confidence interval 1·26-1·33, P < 0·001, respectively). Cutaneous manifestations were also more common with Delta vs. Omicron (17·6% vs. 11·4%, respectively) and had a longer duration. During both waves, cutaneous symptoms clustered with other frequent symptoms and rarely (in < 2% of the users) as first or only clinical sign of SARS-CoV-2 infection. Finally, we observed that vaccinated and unvaccinated users showed similar odds of presenting with a cutaneous manifestation, apart from burning rash, where the odds were lower in vaccinated users.Cutaneous manifestations are predictive of SARS-CoV-2 infection, and their frequency and duration have changed with different variants. Therefore, we advocate for their inclusion in the list of clinically relevant COVID-19 symptoms and suggest that their monitoring could help identify new variants. What is already known about this topic? Several studies during the wildtype COVID-19 wave reported that patients presented with common skin-related symptoms. It has been observed that COVID-19 symptoms differ among variants. No study has focused on how skin-related symptoms have changed across different variants. What does this study add? We showed, in a community-based retrospective study including over 348 000 individuals, that the presence of cutaneous symptoms is predictive of SARS-CoV-2 infection during the Delta and Omicron waves and that this diagnostic value, along with symptom frequency and duration, differs between variants. We showed that infected vaccinated and unvaccinated individuals reported similar skin-related symptoms during the Delta and Omicron waves, with only burning rashes being less common after vaccination.
Amyloid‐Mediated Remineralization in Pit and Fissure for Caries Preventive Therapy
Authors: Xiaoxue Yang, Jing Guo, Bowen Hu, Zihan Li, Meiling Wu, Hao Guo, Xiaoyao Huang, Xuemei Liu, Xiaohe Guo, Peisheng Liu, Yuan Chen, Shijie Li, Yang Gu, Hong Wu, Kun Xuan, Peng Yang
Journal: Advanced Healthcare Materials (2022)

The pits and fissures of teeth have high caries susceptibility, and sealing these areas is considered as an effective method to prevent caries. However, long-term caries prophylaxis cannot be maintained because of the negative effects derived from the technical sensitivity and disadvantages of sealing materials. Herein, a new strategy is proposed to occlude fossae by amyloid-mediated biomimetic remineralization. In contrast to conventional inward blocking from the outside of fossae, amyloid-mediated biomimetic mineralization delivers an amyloid-like protein nanofilm into the deepest zone of the fossae and induces the formation of remineralized enamel inside. Such assembly from lysozyme conjugated with poly (ethylene glycol) enriches the interface with strongly bonded ionsand directs in situ nucleation to achieve enamel epitaxial growth. Not only is the structure of the enamel-like crystalline hydroxyapatite layer but also its mechanical stability is similar to that of natural enamel. Furthermore, the layer shows good biocompatibility and antibacterial properties. On the basis of the findings, it is demonstrated that amyloid-like protein aggregation may provide an enamel remineralization strategy to modify the current clinically available methods of pit and fissure sealing and shows great promise in preventing caries.
Neural substrates of motivational dysfunction across neuropsychiatric conditions: Evidence from meta-analysis and lesion network mapping
Authors: Chunliang Feng, Wenhao Huang, Kangli Xu, Jennifer L. Stewart, Julia A. Camilleri, Xiaofeng Yang, Ping Wei, Ruolei Gu, Wenbo Luo, Simon B. Eickhoff
Journal: Clinical Psychology Review (2022)
Targeted decrease of portal hepatic pressure gradient improves ascites control after TIPS
Authors: Alexander Queck, Louise Schwierz, Wenyi Gu, Philip G. Ferstl, Christian Jansen, Frank E. Uschner, Michael Praktiknjo, Johannes Chang, Maximilian J. Brol, Filippo Schepis, Manuela Merli, Christian P. Strassburg, Jennifer Lehmann, Carsten Meyer, Jonel Trebicka
Journal: Hepatology (2022)

Background: Ascites is a definitive sign of decompensated liver cirrhosis driven by portal hypertension. Although transjugular intrahepatic portosystemic shunt insertion (TIPS) is indicated for therapy of recurrent and refractory ascites, there is no evidence‐based recommendation for a specific target of portal hepatic pressure gradient (PPG) decrease. Methods: In this single‐center, retrospective trial, we investigated the decrease of PPG in 341 patients undergoing TIPS insertion for therapy of refractory or recurrent ascites until 2015. During each procedure, portal and inferior vena cava pressures were invasively measured and correlated with patients' outcome and ascites progression over time, according to the prespecified Noninvasive Evaluation Program for TIPS and Follow‐Up Network protocol (NCT03628807). Results: Patients without ascites at 6 weeks after TIPS had significantly greater PPG reduction immediately after TIPS, compared to the patients with refractory ascites (median reduction 65% vs. 55% of pre‐TIPS PPG; p = 0.001). Survival was significantly better if ascites was controlled, compared to patients with need for paracentesis 6 weeks after TIPS (median survival: 185 vs. 41 weeks; HR 2.0 [1.3–2.9]; p &lt; 0.001). Therefore, higher PPG reduction by TIPS ( p = 0.005) and lower PPG after TIPS ( p = 0.02) correlated with resolution of severe ascites 6 weeks after TIPS. Multivariable analyses demonstrated that higher Child‐Pugh score before TIPS (OR 1.3 [1.0–1.7]; p = 0.03) and lower serum sodium levels (OR 0.9 [0.9–1.0]; p = 0.004) were independently associated with ascites persistence 6 weeks after TIPS, whereas PPG reduction (OR 0.98 [0.97–1.00]; p = 0.02) was associated with resolution of ascites 6 weeks after TIPS. Conclusion: Extent of PPG reduction and/or lowering of target PPG immediately after TIPS placement is associated with improved ascites control in the short term and with survival in the long term. A structured follow‐up visit for patients should assess persistence of ascites at 6 weeks after TIPS.
Polymer Skulls With Integrated Transparent Electrode Arrays for Cortex‐Wide Opto‐Electrophysiological Recordings
Authors: Preston D. Donaldson, Zahra S. Navabi, Russell E. Carter, Skylar M. L. Fausner, Leila Ghanbari, Timothy J. Ebner, Sarah L. Swisher, Suhasa B. Kodandaramaiah
Journal: Advanced Healthcare Materials (2022)

Electrophysiology and optical imaging provide complementary neural sensing capabilities - electrophysiological recordings have high temporal resolution, while optical imaging allows recording of genetically-defined populations at high spatial resolution. Combining these two modalities for simultaneous large-scale, multimodal sensing of neural activity across multiple brain regions can be very powerful. Here, transparent, inkjet-printed electrode arrays with outstanding optical and electrical properties are seamlessly integrated with morphologically conformant transparent polymer skulls. Implanted on transgenic mice expressing the Calcium (Ca
Measurable Residual Disease Testing in Acute Leukemia: Technology and Clinical Significance
Authors: Weijie Li
Journal: Leukemia (2022)

Measurable/minimal residual disease (MRD) is the strongest independent prognostic predictor in acute leukemia. Patients with undetectable MRD or good MRD response consistently demonstrate a lower risk of relapse and better survival outcomes compared with similarly treated patients with positive MRD or poor MRD response. MRD has already been used to guide risk-adapted therapies in routine care of patients with acute leukemia or in clinical trials in many countries. MRD can also be used as a surveillance biomarker with the potential to detect early relapse, and as a surrogate endpoint to speed up the testing and approval process for a new therapeutic agent. Multi-parametric flow cytometry and quantitative PCR are two methods commonly used for MRD detection. Recently, new techniques, such as digital PCR, next-generation sequencing, and next-generation flow cytometry, have also been applied in MRD detection and showed improved sensitivity and accuracy. These methods have their own advantages and limitations. Despite tremendous advances in this field, there are still issues and questions regarding MRD testing methods and how to translate MRD information accurately into clinical and therapeutic applications. This chapter gives an overview of the methods and the clinical implications of MRD testing in acute lymphoblastic leukemia and acute myeloid leukemia.
Exposure to avian coronavirus vaccines is associated with increased levels of <scp>SARS‐CoV</scp>‐2‐cross‐reactive antibodies
Authors: Ozge Ardicli, K. Tayfun Carli, Pattraporn Satitsuksanoa, Anita Dreher, Alexia Cusini, Sandra Hutter, David Mirer, Beate Rückert, Hulda R. Jonsdottir, Benjamin Weber, Carlo Cervia, Mubeccel Akdis, Onur Boyman, Alexander Eggel, Marie‐Charlotte Brüggen, Cezmi A. Akdis, Willem van de Veen
Journal: Allergy (2022)

Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines.We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed.A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT.We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19.
Incretin-Based Drugs and the Risk of Acute Liver Injury Among Patients With Type 2 Diabetes
Authors: Richeek Pradhan, Hui Yin, Oriana H.Y. Yu, Laurent Azoulay
Journal: Diabetes Care (2022)

OBJECTIVE To determine whether the use of dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs), separately, is associated with an increased risk of acute liver injury compared with the use of sodium–glucose cotransporter 2 (SGLT-2) inhibitors. RESEARCH DESIGN AND METHODS We used the U.K. Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and the Office for National Statistics databases to assemble two new-user, active-comparator cohorts. The first included 106,310 initiators of DPP-4 inhibitors and 27,277 initiators of SGLT-2 inhibitors, while the second included 9,470 initiators of GLP-1 RAs and 26,936 initiators of SGLT-2 inhibitors. Cox proportional hazards models with propensity score fine stratification weighting were used to estimate hazard ratios (HRs) and 95% CIs of acute liver injury. RESULTS Compared with SGLT-2 inhibitors, DPP-4 inhibitors were associated with a 53% increased risk of acute liver injury (HR 1.53, 95% CI 1.02–2.30). In contrast, GLP-1 RAs were not associated with an overall increased risk of acute liver injury (HR 1.11, 95% CI 0.57–2.16). However, an increased risk was observed among female users of both DPP-4 inhibitors (HR 3.22, 95% CI 1.67–6.21) and GLP-1 RAs (HR 3.23, 95% CI 1.44–7.25). CONCLUSIONS In this population-based study, DPP-4 inhibitors were associated with an increased risk of acute liver injury compared with SGLT-2 inhibitors in patients with type 2 diabetes. In contrast, an increased risk of acute liver injury was observed only among female GLP-1 RA users.
WNT Medulloblastoma Limbo: How Low Can We Go?
Authors: Marc Remke, Vijay Ramaswamy
Journal: Clinical Cancer Research (2022)

Survival rates for average-risk medulloblastoma exceed 80%; however, long-term sequelae are substantial. A study from Mumbai, India evaluated the role of omission of craniospinal irradiation. Albeit unsuccessful, this study raises the crucial question of how low therapy can be safely de-escalated with the intent of improving quality of survival. See related article by Gupta et al., p. 4180.
Gain-of-function mutations in<i>ALPK1</i>cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome
Authors: Christina Torres Kozycki, Shilpa Kodati, Laryssa Huryn, Hongying Wang, Blake M Warner, Priyam Jani, Dima Hammoud, Mones S Abu-Asab, Yingyos Jittayasothorn, Mary J Mattapallil, Wanxia Li Tsai, Ehsan Ullah, Ping Zhou, Xiaoying Tian, Ariane Soldatos, Niki Moutsopoulos, Marie Kao-Hsieh, Theo Heller, Edward W Cowen, Chyi-Chia Richard Lee, Camilo Toro, Shelley Kalsi, Zohreh Khavandgar, Alan Baer, Margaret Beach, Debra Long Priel, Michele Nehrebecky, Sofia Rosenzweig, Tina Romeo, Natalie Deuitch, Laurie Brenchley, Eileen Pelayo, Wadih Zein, Nida Sen, Alexander H Yang, Gary Farley, David A Sweetser, Lauren Briere, Janine Yang, Fabiano de Oliveira Poswar, Ida Vanessa D Schwartz, Tamires Silva Alves, Perrine Dusser, Isabelle Koné-Paut, Isabelle Touitou, Salah Mohamed Titah, Petrus Martin van Hagen, Rogier T A van Wijck, Peter J van der Spek, Hiromi Yano, Andreas Benneche, Ellen M Apalset, Ragnhild Wivestad Jansson, Rachel R Caspi, Douglas Byron Kuhns, Massimo Gadina, Hidetoshi Takada, Hiroaki Ida, Ryuta Nishikomori, Elena Verrecchia, Eugenio Sangiorgi, Raffaele Manna, Brian P Brooks, Lucia Sobrin, Robert B Hufnagel, David Beck, Feng Shao, Amanda K Ombrello, Ivona Aksentijevich, Daniel L Kastner
Journal: Annals of the Rheumatic Diseases (2022)

To test the hypothesis that ROSAH (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis and headache) syndrome, caused by dominant mutation in